Referat Bone Sarcoma (Zihan Aulia Nugraha)

688
NCCN Overview
Bone Cancer Primary bone cancers are extremely rare neoplasms

accounting for fewer than 0.2% of all cancers, al-
though the true incidence is difficult to determine
Clinical Practice Guidelines in Oncology because of the rarity of these tumors.1,2 In 2013,
J. Sybil Biermann, MD; Douglas R. Adkins, MD; an estimated 3010 new cases will be diagnosed in
Mark Agulnik, MD; Robert S. Benjamin, MD; the United States and 1440 people will die of the
Brian Brigman, MD, PhD; James E. Butrynski, MD; disease.3 Primary bone cancers demonstrate wide
David Cheong, MD; Warren Chow, MD; William T. Curry, MD;
Deborah A. Frassica, MD; Frank J. Frassica, MD;
clinical heterogeneity and are often curable with
Kenneth R. Hande, MD; Francis J. Hornicek, MD, PhD; proper treatment. Osteosarcoma (35%), chondro-
Robin L. Jones, MD, BS, MRCP; Joel Mayerson, MD; sarcoma (30%), and Ewing sarcoma (16%) are the
Sean V. McGarry, MD; Brian McGrath, MD; most common forms of bone cancer. Malignant fi-
Carol D. Morris, MD, MS; Richard J. O’Donnell, MD;
R. Lor Randall, MD; Victor M. Santana, MD;
brous histiocytoma, fibrosarcoma, chordoma, and
Robert L. Satcher, MD, PhD; Herrick J. Siegel, MD; giant cell tumor of the bone (GCTB) are rare tu-
Margaret von Mehren, MD; Mary Anne Bergman; and mors, constituting up to 1% to 5% of all primary
Hema Sundar, PhD malignant bone tumors.4 GCTB has both benign
Abstract Please Note

Primary bone cancers are extremely rare neoplasms, account- The NCCN Clinical Practice Guidelines in Oncology
ing for fewer than 0.2% of all cancers. The evaluation and
(NCCN Guidelines®) are a statement of consensus of the
treatment of patients with bone cancers requires a multidis-
authors regarding their views of currently accepted ap-
ciplinary team of physicians, including musculoskeletal, medi-
cal, and radiation oncologists, and surgeons and radiologists
proaches to treatment. Any clinician seeking to apply or
with demonstrated expertise in the management of these consult the NCCN Guidelines® is expected to use inde-
tumors. Long-term surveillance and follow-up are necessary pendent medical judgment in the context of individual
for the management of treatment late effects related to sur- clinical circumstances to determine any patient’s care or
gery, radiation therapy, and chemotherapy. These guidelines treatment. The National Comprehensive Cancer Net-
discuss the management of chordoma, giant cell tumor of the work® (NCCN®) makes no representation or warranties
bone, and osteosarcoma. (JNCCN 2013;11:688–723) of any kind regarding their content, use, or application
NCCN Categories of Evidence and Consensus and disclaims any responsibility for their applications or
Category 1: Based upon high-level evidence, there is uni- use in any way. The full NCCN Guidelines for Bone
form NCCN consensus that the intervention is appropri- Cancer are not printed in this issue of JNCCN but can
ate. be accessed online at NCCN.org.
Category 2A: Based upon lower-level evidence, there is © National Comprehensive Cancer Network, Inc.
uniform NCCN consensus that the intervention is appro- 2013, All rights reserved. The NCCN Guidelines and the
priate. illustrations herein may not be reproduced in any form
Category 2B: Based upon lower-level evidence, there is without the express written permission of NCCN.
NCCN consensus that the intervention is appropriate. Disclosures for the NCCN Bone Cancer Panel
Category 3: Based upon any level of evidence, there is
At the beginning of each NCCN Guidelines panel meeting, panel
major NCCN disagreement that the intervention is ap-
members review all potential conflicts of interest. NCCN, in keep-
propriate. ing with its commitment to public transparency, publishes these
All recommendations are category 2A unless otherwise disclosures for panel members, staff, and NCCN itself.
noted.
Individual disclosures for the NCCN Bone Cancer Panel members
Clinical trials: NCCN believes that the best management for can be found on page 723. (The most recent version of these
any cancer patient is in a clinical trial. Participation in clinical guidelines and accompanying disclosures are available on the
trials is especially encouraged. NCCN Web site at NCCN.org.)
These guidelines are also available on the Internet. For the

latest update, visit NCCN.org.
© JNCCN—Journal of the National Comprehensive Cancer Network | Volume 11 Number 6 | June 2013
689
NCCN
Guidelines®
Journal of the National Comprehensive Cancer Network Bone

Cancer
and malignant forms, with the benign form the The pathogenesis and origin of most bone
most common subtype. cancers remains unclear. Gene rearrangements
Various types of bone cancers are named based between the EWS and ETS family of genes have
on their histologic origin: chondrosarcomas arise been implicated in the pathogenesis of ESFT.7–10
from cartilage, osteosarcomas arise from bone, and Specific germ-line mutations have also been impli-
fibrogenic tissue is the origin of fibrosarcoma of bone, cated in the pathogenesis of osteosarcoma.11,12 The
whereas vascular tissue gives rise to hemangioendo- Li-Fraumeni syndrome characterized by a germ-line
thelioma and hemangiopericytoma. Notochordal mutation in the TP53 gene is associated with a high
tissue gives rise to chordoma. Several primary bone risk of developing osteosarcoma.13–15 Osteosarcoma
cancers, including Ewing sarcoma family of tumors is the most common second primary malignancy in
(ESFT), are of unknown histologic origin. Chondro- patients with a history of retinoblastoma, charac-
sarcoma is usually found in middle-aged and older terized by a mutation in the retinoblastoma gene
adults. Osteosarcoma and Ewing sarcoma develop RB1.11,16,17 Increased incidences of osteosarcoma
mainly in children and young adults. Chordoma is have also been associated with other inherited ge-
more common in men, with peak incidence in the netic predisposition syndromes characterized by
fifth to sixth decades of life.5,6 mutations in the DNA helicase genes.11,12 Osteosar-
Text continues on p. 706
NCCN Bone Cancer Panel Members Joel Mayerson, MD¶τ

The Ohio State University Comprehensive Cancer Center –
*J. Sybil Biermann, MD/Chair¶τ
University of Michigan Comprehensive Cancer Center James Cancer Hospital and Solove Research Institute
Douglas R. Adkins, MD† Sean V. McGarry, MDτ
Siteman Cancer Center at Barnes-Jewish Hospital and UNMC Eppley Cancer Center at
Washington University School of Medicine The Nebraska Medical Center
Mark Agulnik, MD† Brian McGrath, MD
Robert H. Lurie Comprehensive Cancer Center of Roswell Park Cancer Institute
Northwestern University *Carol D. Morris, MD, MS¶τ
Robert S. Benjamin, MD† Memorial Sloan-Kettering Cancer Center
The University of Texas MD Anderson Cancer Center
Richard J. O’Donnell, MD¶τ
Brian Brigman, MD, PhD¶τ
UCSF Helen Diller Family Comprehensive Cancer Center
Duke Cancer Institute
R. Lor Randall, MD¶τ
*James E. Butrynski, MD†‡
Dana-Farber/Brigham and Women’s Cancer Center Huntsman Cancer Institute at the University of Utah
David Cheong, MD Victor M. Santana, MD€
Moffitt Cancer Center St. Jude Children’s Research Hospital/
*Warren Chow, MD†‡ University of Tennessee Health Science Center
City of Hope Comprehensive Cancer Center Robert L. Satcher, MD, PhD¶τ
William T. Curry, MD¶ The University of Texas MD Anderson Cancer Center
Massachusetts General Hospital Cancer Center Herrick J. Siegel, MD¶τ
Deborah A. Frassica, MD§
University of Alabama at Birmingham
The Sidney Kimmel Comprehensive Cancer Center at
Comprehensive Cancer Center
Johns Hopkins
Margaret von Mehren, MD†
Frank J. Frassica, MD¶τ
The Sidney Kimmel Comprehensive Cancer Center at Fox Chase Cancer Center
Johns Hopkins NCCN Staff: Mary Anne Bergman and Hema Sundar, PhD
Kenneth R. Hande, MD† KEY:
Vanderbilt-Ingram Cancer Center *Writing Committee Member
*Francis J. Hornicek, MD, PhDτ€
Massachusetts General Hospital Cancer Center Specialties: ¶Surgery/Surgical Oncology; †Medical
*Robin L. Jones, MD, BS, MRCP† Oncology; ‡Hematology/Hematology Oncology; §Radio-
Fred Hutchinson Cancer Research Center/ therapy/Radiation Oncology; τOrthopedics; €Pediatric
Seattle Cancer Care Alliance Oncology
© JNCCN–Journal of the National Comprehensive Cancer Network | Volume 11 Number 6 | June 2013
690
CHORDOMA Bone Cancer, Version 2.2013
WORKUP a,b HISTOLOGIC SUBTYPE
Conventional See Presentation and

or Primary Treatment
Chondroid (facing page)
• All patients should be evaluated and treated by a
multidisciplinary team with expertise in the
management of chordoma a
• History and physical
• Adequate imaging (eg, x-ray, CT ± MRI) of primary
site and screening MRI of spinal axis
• CT scan of chest, abdomen, and pelvis
• Consider PET scan
• Consider bone scan if PET is negative
• Biopsy to confirm histologic subtype b,c
See NCCN Guidelines for
Soft Tissue Sarcoma (to
Dedifferentiated
view the most recent
version of these
guidelines, visit NCCN.org)
a See Multidisciplinary Team (page 700).

b See Principles of Bone Cancer Management (page 701).
c Biopsy should be done after imaging studies are completed; biopsy type may vary depending on anatomic location. Optimally, biopsy should be performed
at a center of excellence where definitive management is given. Cord compression may limit surgical procedures.
CHOR-1
Clinical trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. All
recommendations are category 2A unless otherwise indicated.
691
NCCN Clinical Practice Guidelines in Oncology
Bone Cancer, Version 2.2013 CHORDOMA
PRESENTATION PRIMARY TREATMENT ADJUVANT TREATMENT
Consider RT d,e
Wide resection b for positive surgical
± RT, d,e margins or for large
if resectable
extracompartmental
tumors
Sacrococcygeal
and OR
Mobile spine
Consider RT e
if unresectable
See Surveillance
(page 692)
Follow-up
• Consider RT d,e
for positive surgical
Intralesional excision f MRI to
margins or for large
± RT, d,e assess
extracompartmental
if resectable adequacy of
tumors
resection
• Consider re-resection
if necessary
Skull base/Clival OR
Consider RT e
if unresectable

d Radiation therapy may be given preoperatively, intraoperatively, and/or postoperatively.
e See Principles of Radiation Therapy (pages 704-705).
f Maximal safe resection. Maximal tumor removal is recommended when appropriate.
CHOR-2
Version 2.2013, 01-31-13 ©2013 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be
reproduced in any form without the express written permission of NCCN®.
692
CHORDOMA Bone Cancer, Version 2.2013
SURVEILLANCE RECURRENCE TREATMENT
Surgical excision b
Local recurrence and/or
RT e
and/or
• Physical exam Systemic therapy g
• Imaging (eg, x-ray, CT ± MRI)
of surgical site as clinically
indicated
• Chest imaging every 6 mo
for 5 y, then annually
thereafter
• Cross-sectional abdominal
imaging annually
Systemic therapy g
and/or
Metastatic Surgical excision b
recurrence and/or
RT e
Best supportive care

e See Principles of Radiation Therapy (pages 704-705).
g See Bone Cancer Systemic Therapy Agents (pages 702-703).
CHOR-3
693
Bone Cancer, Version 2.2013 GIANT CELL TUMOR OF THE BONE
WORKUP PRESENTATION
Localized disease
• History and physical examination

• Imaging (eg, x-ray, MRI ± CT) of
primary site See page 694
• Chest imaging
• Bone scan (optional)
• Biopsy to confirm diagnosis a,b
• If there is malignant transformation,
treat as described for osteosarcoma
(See page 696)
Metastatic disease
at presentation
a Brown tumor of hyperparathyroidism should be considered as a differential diagnosis.

GCTB-1
694
GIANT CELL TUMOR OF THE BONE Bone Cancer, Version 2.2013
PRIMARY TREATMENT
Resectable Excision c
Stable/Improved
disease
Localized
disease
Changes to
resectable Excision c See
Serial Surveillance
Resectable (facing
with embolization
and/or Stable/Improved page)
unacceptable Denosumab d,e disease with
morbidity and/or incomplete
and/or IFN e or PEG IFN e
Unresectable healing
and/or
axial lesions RT f,h
Remains Continue
unresectable denosumab
Progressive
disease
See Primary Treatment for Localized Disease,

Resectable above, for the treatment of primary tumor
Consider excision c of metastatic sites
Metastatic
disease at
See
presentation g
Surveillance
Consider the following options: (facing page)
• Denosumab
Unresectable • IFN e or PEG IFN e
• RT h
• Observation
c Intralesional excision, with an effective adjuvant is adequate.

d Denosumab should be continued until disease progression in responding patients.
e See Bone Cancer Systemic Therapy Agents (pages 702-703).
f RT has been associated with increased risk of malignant transformation.
g Treatment of primary tumor is as described for localized disease.
h See Principles of Radiation Therapy (pages 704-705).
GCTB-2
695
Bone Cancer, Version 2.2013 GIANT CELL TUMOR OF THE BONE
SURVEILLANCE RECURRENCE
Consider
Consider chest denosumab prior
Resectable to surgery
imaging
(see previous
page)
Local recurrence
• Physical exam
• Imaging (x-ray, MRI ± CT) Resectable
of surgical site as clinically with unacceptable
morbidity
indicated or
• Chest imaging every 6 mo unresectable
for 2 years then annually axial lesions
thereafter
See previous page
Metastatic
recurrence
GCTB-3
696
OSTEOSARCOMA Bone Cancer, Version 2.2013
WORKUP a,b PRIMARY TREATMENT ADJUVANT TREATMENT
High Chemotherapy d
Low-grade osteosarcoma: c Wide
Intramedullary + surface excision b grade (category 2B)
See
• History and Surveillance
physical (page 699)
• MRI ± CT of
primary site
• Chest imaging Periosteal Consider Wide Low
including osteosarcoma chemotherapy d excision b grade
chest CT
• PET scan
and/or bone
scan
• MRI or
CT of
skeletal
metastatic
sites e High-grade
• LDH osteosarcoma: See facing page
• ALP Intramedullary
+ surface
• Fertility
consultation
as appropriate
Metastatic disease See facing page

at presentation
a See Multidisciplinary Team (page 700).

c Dedifferentiated parosteal osteosarcomas are not considered to be low-grade tumors.
d See Bone Cancer Systemic Therapy Agents (pages 702-703).
e More detailed imaging (CT or MRI) of abnormalities identified on primary imaging is required for suspected metastatic disease.
OSTEO-1
697
Bone Cancer, Version 2.2013 OSTEOSARCOMA
NEOADJUVANT
RESTAGE ADJUVANT TREATMENT
TREATMENT
RT h
Unresectable
Chemotherapy d
Reassess
tumor as • Chemotherapy d
appropriate • Consider
Restage with Good
additional local
pretreatment response g
High-grade therapy (surgical
Preoperative imaging
osteosarcoma: chemotherapy d,f resection ± RT) h
Intramedullary modalities:
+ surface (category 1)
• Chest Positive
imaging margins
• Imaging of
primary site Consider
• Consider additional local
PET scan Poor therapy (surgical See
or response g resection ± RT) h Surveillance
bone scan Consider (page 699)
changing
Wide chemotherapy d
Resectable excision b
Good Chemotherapy d
response g
Negative
margins
Consider
Poor
changing
response g
chemotherapy d

f Selected elderly patients may benefit from immediate surgery.
g Response is defined by pathologic mapping per institutional guidelines; the amount of viable tumor is reported as <10% of the tumor area in cases showing
a good response and10% in cases showing a poor response.
OSTEO-2
698
OSTEOSARCOMA Bone Cancer, Version 2.2013
PRIMARY TREATMENT
• See page 697 for

management of
Resectable (pulmonary,
primary tumor
visceral, or skeletal metastases)
• Chemotherapy d
• Metastasectomy
Surveillance
Metastatic disease
(See page 699)
• Chemotherapy d
• RT h
Unresectable • Reassess primary site
as appropriate for
local control

OSTEO-3
699
Bone Cancer, Version 2.2013 OSTEOSARCOMA
SURVEILLANCE RELAPSE
Response Surveillance
• Chest imaging
• CBC and other laboratory
studies as indicated
• Imaging of primary site i
• Consider PET scan and/or
bone scan (category 2B) Chemotherapy d
• Reassess function every visit and/or
• Follow-up schedule: Relapse
resection
(Orthopedic and Oncologic) if possible
➤ Every 3 mo for year 1 and 2 Resection, if possible
➤ Every 4 mo for year 3 or
➤ Every 6 mo for year 4 and 5
Best supportive care
or
and yearly thereafter Clinical trial
or
Relapse/ Samarium-153 ethylene
Progression diamine tetramethylene
phosphonate
( 153 Sm-EDTMP)
or
Palliative RT

i Use the same imaging technique that was performed in the initial workup.
OSTEO-4
700
Bone Cancer, Version 2.2013
MULTIDISCIPLINARY TEAM
Primary bone tumors and selected metastatic tumors should be evaluated and treated by a multidisciplinary team with
expertise in the management of these tumors. The team should meet on a regular basis and should include:
Core Group
Musculoskeletal oncologist
Bone pathologist
Medical/pediatric oncologist
Radiation oncologist
Musculoskeletal radiologist
Specialists Critical in Certain Cases

Thoracic surgeon
Plastic surgeon
Interventional radiologist
Physiatrist
Vascular/general surgeon
Neurosurgeon
Additional surgical subspecialties as clinically indicated
BONE-A
701
PRINCIPLES OF BONE CANCER MANAGEMENT
Biopsy
Biopsy diagnosis is necessary before any surgical procedure or fixation of primary site.
Biopsy is optimally performed at a center that will do definitive management.
Placement of biopsy is critical.
Biopsy should be core needle or surgical biopsy.
Technique: apply same principles for core needle or open biopsy. Needle biopsy is not recommended for skull base tumors.
Appropriate communication between the surgeon, musculoskeletal radiologist, and bone pathologist is critical.
Fresh tissue may be needed for molecular studies and tissue banking.
In general, failure to follow appropriate biopsy procedures may lead to adverse patient outcomes.
Final pathological evaluation should include assessment of surgical margins and size/dimensions of tumor.
Surgery
Wide excision should achieve histologically negative surgical margins.
Negative surgical margins optimize local tumor control.
Local tumor control may be achieved by either limb-sparing resection or limb amputation (individualized for a given patient).
Limb-sparing resection is preferred to optimize function if reasonable functional expectations can be achieved.
Laboratory Studies
Laboratory studies such as CBC, LDH, and ALP may have relevance in the diagnosis, prognosis, and management of
patients with bone sarcoma and should be performed before definitive treatment and periodically during treatment and
surveillance.
Treatment
Fertility issues should be addressed with patients prior to commencing chemotherapy.
Care for bone cancer patients should be delivered directly by physicians on the multidisciplinary team (category 1).
(See previous page)
Long-Term Follow-up and Surveillance/Survivorship

Patients should have a survivorship prescription to schedule follow-up with a multidisciplinary team.
Lifelong follow-up is recommended for surveillance and treatment of late effects of surgery, radiation, and chemotherapy in
long-term survivors.
BONE-B
702
BONE CANCER SYSTEMIC THERAPY AGENTS
Chordoma
➤ Imatinib 1,2
➤ Imatinib with cisplatin 3 or sirolimus 4
➤ Erlotinib 5
➤ Erlotinib + cetuximab 6
➤ Sunitinib 7
Giant Cell Tumor of Bone

➤ Denosumab 8-10
➤ Interferon alfa 11-13
➤ Peginterferon 13
Osteosarcoma †
• First-line therapy (primary/neoadjuvant/adjuvant therapy or metastatic disease)
➤ Cisplatin and doxorubicin 14-16
➤ MAP (High-dose methotrexate, cisplatin, and doxorubicin) 17,18
➤ Doxorubicin, cisplatin, ifosfamide, and high-dose methotrexate 19
➤ Ifosfamide, cisplatin, and epirubicin 20
• Second-line therapy (relapsed/refractory or metastatic disease)

➤ Docetaxel and gemcitabine 21
➤ Cyclophosphamide and etoposide 22
➤ Cyclophosphamide and topotecan 23
➤ Gemcitabine 24
➤ Ifosfamide and etoposide 25
➤ Ifosfamide, carboplatin, and etoposide 26
➤ High-dose methotrexate, etoposide, and ifosfamide 27
➤
153
Sm-EDTMP for relapsed or refractory disease beyond second-line therapy 28
➤ Sorafenib 29

(References)
1 Geoerger B, Morland B, Ndiaye A, et al. Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the
Innovative Therapies for Children with Cancer (ITCC) European Consortium. Eur J Cancer 2009;45:2342-2351.
2 Casali PG, Messina A, Stacchiotti S, et al. Imatinib mesylate in chordoma. Cancer 2004;101:2086-2097.
3 Casali PG, Stacchiotti S, Grosso F, et al. Adding cisplatin (CDDP) to imatinib (IM) re-establishes tumor response following secondary
resistance to IM in advanced chordoma [abstract]. J Clin Oncol 2007;25(18 Suppl):Abstract 10038.
4 Stacchiotti S, Marrari A, Tamborini E, et al. Response to imatinib plus sirolimus in advanced chordoma. Ann Oncol 2009;20:1886-1894.
5 Singhal N, Kotasek D, Parnis FX. Response to erlotinib in a patient with treatment refractory chordoma. Anticancer Drugs 2009;20:953-
955.
6 Linden O, Ehinger M, Kinhult S, et al. Cetuximab and EGFR inhibitors in patients with neurological symptoms due to chordoma [abstract].
J Clin Oncol 2012;30(Suppl):Abstract 10024.
7 George S, Merriam P, Maki RG, et al. Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas.
J Clin Oncol 2009;27:3154-3160.
8 Blay J, Chawla SP, Martin Broto J, et al. Denosumab safety and efficacy in giant cell tumor of bone (GCTB): Interim results from a phase
II study [abstract]. J Clin Oncol 2011;29(Suppl):Abstract 10034.
9 Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of
bone. Clin Cancer Res 2012;18:4415-4424.
10 Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet
Oncol 2010;11:275-280.
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(References Cont.)
11 Kaiser U, Neumann K, Havemann K. Generalised giant-cell tumour of bone: successful treatment of pulmonary metastases with
interferon alpha, a case report. J Cancer Res Clin Oncol 1993;119:301-303.
12 Kaban LB, Troulis MJ, Ebb D, et al. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg
2002;60:1103-1111.
13 Yasko AW. Interferon therapy for giant cell tumor of bone. Curr Opin Orthop 2006;17:568-572.
14 Bramwell V, Burgers M, Sneath R, et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable
osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol
1992;10:1579-1591.
15 Lewis IJ, Nooij MA, Whelan J, et al. Improvement in histologic response but not survival in osteosarcoma patients treated with
intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst 2007;99:112-128.
16 Souhami RL, Craft AW, Van der Eijken JW, et al. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study
of the European Osteosarcoma Intergroup. Lancet 1997;350:911-917.
17 Bacci G, Ferrari S, Bertoni F, et al. Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the
istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report. J Clin Oncol
2000;18:4016-4027.
18 Winkler K, Beron G, Delling G, et al. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82)
with salvage chemotherapy based on histological tumor response. J Clin Oncol 1988;6:329-337.
19 Bacci G, Briccoli A, Rocca M, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation:
recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and
ifosfamide. Ann Oncol 2003;14:1126-1134.
20 Basaran M, Bavbek ES, Saglam S, et al. A phase II study of cisplatin, ifosfamide and epirubicin combination chemotherapy in adults
with nonmetastatic and extremity osteosarcomas. Oncology 2007;72:255-260.
21 Navid F, Willert JR, McCarville MB, et al. Combination of gemcitabine and docetaxel in the treatment of children and young adults with
refractory bone sarcoma. Cancer 2008;113:419-425.
22 Berger M, Grignani G, Ferrari S, et al. Phase 2 trial of two courses of cyclophosphamide and etoposide for relapsed high-risk
osteosarcoma patients. Cancer 2009;115:2980-2987.
23 Saylors RL 3rd, Stine KC, Sullivan J, et al. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a
Pediatric Oncology Group phase II study. J Clin Oncol 2001;19:3463-3469.
24 Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in
patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J Clin Oncol
2007;25:2755-2763.
25 Miser JS, Kinsella TJ, Triche TJ, et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of
recurrent sarcomas and other tumors of children and young adults. J Clin Oncol 1987;5:1191-1198.
26 Van Winkle P, Angiolillo A, Krailo M, et al. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of
children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer
2005;44:338-347.
27 Le Deley MC, Guinebretiere JM, Gentet JC, et al. SFOP OS94: a randomised trial comparing preoperative high-dose methotrexate plus
doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients. Eur J Cancer 2007;43:752-761.
28 Anderson PM, Wiseman GA, Dispenzieri A, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity
of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 2002;20:189-196.
29 Grignani G, Palmerini E, Dileo P, et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of
standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol 2012;23:508-516.
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PRINCIPLES OF RADIATION THERAPY
Patients should be strongly encouraged to have radiation therapy at the same specialized center that is providing surgical and systemic
interventions.
Specialized techniques such as intensity-modulated radiation therapy; particle-beam RT with protons, carbon ions, or other heavy ions;
stereotactic radiosurgery; or fractionated stereotactic radiotherapy should be considered as indicated to allow
high-dose therapy while maximizing normal tissue-sparing.
CHORDOMA
Base of Skull
➤ Postoperative RT (R1 and R2 resection) 1 or RT for unresectable disease - >70 Gy
➤ Consider postoperative RT for R0 resections
Mobile Spine
➤ Consider preoperative RT (19.8-50.4 Gy) and postoperative RT to total dose of 70 Gy (depending on normal tissue tolerances)
GIANT CELL TUMOR OF BONE

Treatment of Metastatic Disease
Consider RT (50-60 Gy) for unresectable/progressive/recurrent disease that has not responded to serial embolizations,
denosumab, IFN, or pegylated IFN.
An increased risk of malignant transformation following RT has been noted in some studies.
OSTEOSARCOMA
Treatment of Primary Tumor

RT should be considered for patients with positive margins of resection, subtotal resections, or unresectable disease
➤ Postoperative RT (R1 and R2 resections): 1 55 Gy (64-68 Gy to area of highest risk)
➤ Unresectable disease: 60 - >70 Gy depending on normal tissue tolerance
Treatment of Metastatic Disease
Consider use of 153Sm-EDTMP
Consider use of Stereotactic radiosurgery, especially for oligometastases
1 R0 = No microscopic residual disease, R1 = Microscopic residual disease, R2 = Gross residual disease
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PRINCIPLES OF RADIATION THERAPY

(References)
Chordoma
Amichetti M, Cianchetti M, Amelio D, et al. Proton therapy in chordoma of the base of the skull: a systematic review. Neurosurg Rev
2009;32:403.
Park L, Delaney TF, Liebsch NJ, et al. Sacral chordomas: impact of high-dose proton/photon-beam radiation therapy combined with or
without surgery for primary versus recurrent tumor. Int J Radiat Oncol Biol Phys 2006;65:1514-1521.
Giant Cell Tumor of Bone

Caudell JJ, Ballo MT, Zagars GK, et al. Radiotherapy in the management of giant cell tumor of bone. Int J Radiat Oncol Biol Phys
2003;57:158.
Hug EB, Muenter MW, Adams JA, et al. 3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base. Strahlenther Onkol
2002;178:239.
Malone S, O'Sullivan B, Catton C, et al. Long-term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell
tumors of bone. Int J Radiat Oncol Biol Phys 1995;33:689.
Ruka W, Rutkowski P, Morysiński T, et al. The megavoltage radiation therapy in treatment of patients with advanced or difficult giant cell
tumors of bone. Int J Radiat Oncol Biol Phys 2010;78:494.
Mixed Histology Reports

DeLaney TF, Liebsch NJ, Pedlow FX, et al. Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas.
Int J Radiat Oncol Biol Phys 2009;74:732-739.
Kamada T, Tsujii H, Yanagi T, et al. Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas. Working Group for the
Bone and Soft Tissue Sarcomas. J Clin Oncol 2002;20:4466.
Wagner TD, Kobayashi W, Dean S, et al. Combination short-course preoperative irradiation, surgical resection, and reduced-field high-dose
postoperative irradiation in the treatment of tumors involving the bone. Int J Radiat Oncol Biol Phys 2009;73:259-266.
BONE-D (2 OF 2)
706 NCCN Clinical Practice Guidelines in Oncology
Bone Cancer
Text continued from p. 689
coma is also the most common radiation-induced associated with chemotherapy and radiation therapy
bone sarcoma.18,19 (RT). Life-long follow-up is recommended for sur-
The development of multiagent chemotherapy veillance and treatment of late effects of surgery, RT,
regimens for neoadjuvant and adjuvant treatment and chemotherapy in long-term survivors. Patients
has considerably improved the prognosis for patients should be given a survivorship prescription to sched-
with osteosarcoma and ESFT.20,21 With current mul- ule follow-up with a multidisciplinary team. Fertility
timodality treatment, approximately three-quarters issues should be discussed with appropriate patients
of all patients diagnosed with osteosarcoma are before initiation of treatment.26
cured and 90% to 95% of adult patients diagnosed
with osteosarcoma can be successfully treated with
limb-sparing approaches rather than amputation.22 Diagnostic Workup
Survival rates have improved to almost 70% in pa- Suspicion of a malignant bone tumor in a patient
tients with localized ESFT.21 A cure is still achiev- with a painful lesion often begins when a poorly
able in selected patients diagnosed with metastatic marginated lesion is seen on a plain radiograph. In
ESFT and osteosarcoma at presentation.23,24 patients younger than 40 years, an aggressive, painful
These guidelines focus on chordoma, chon- bone lesion has a significant risk of being a malig-
drosarcoma, ESFT, GCTB, and osteosarcoma. nant primary bone tumor, and referral to an ortho-
This manuscript highlights only a portion of the pedic oncologist should be considered before further
NCCN Clinical Practice Guidelines in Oncology workup. In patients 40 years of age and older, CT
(NCCN Guidelines) for Bone Cancer. Please refer to scan of the chest, abdomen, and pelvis; bone scan;
NCCN.org for the complete version of these guidelines. mammogram; and other imaging studies as clinically
indicated should be performed if plain radiographs
do not suggest a specific diagnosis.27
Staging All patients with suspected bone sarcoma should
The 2010 AJCC staging classification is shown in Ta- undergo complete staging before biopsy. The standard
ble 1 (available online, in these guidelines, at NCCN. staging workup for a suspected primary bone cancer
org [ST-1]). This system is based on the assessment of should include chest imaging (chest radiograph or
histologic grade (G), tumor size (T), and presence of chest CT to detect pulmonary metastases), appropri-
regional (N) and/or distant metastases (M). The Sur- ate imaging of the primary site (plain radiographs, MRI
gical Staging System (SSS) is another staging system for local staging, and/or CT scan), and bone scan.28
for bone and soft tissue sarcomas developed by the Whole-body MRI is a sensitive imaging technique for
Musculoskeletal Tumor Society (Table 2, available at detecting skeletal metastases in patients with small
NCCN.org [ST-1]).25 (available at NCCN.org [ST- cell neoplasms, ESFT, and osteosarcoma.29,30 Imaging
1]).25 This system stratifies both bone and soft tissue of painless bone lesions should be evaluated by a mus-
sarcomas by the assessment of the surgical grade (G), culoskeletal radiologist followed by appropriate refer-
ral to a multidisciplinary treatment team if necessary.
local extent (T), and presence or absence of regional
Laboratory studies, such as CBC, lactate dehydroge-
or distant metastases. It may be used in addition to the
nase (LDH), and alkaline phosphatase (ALP), should
AJCC staging system.
be performed before initiation of treatment.
PET or PET/CT is an alternative imaging tech-
Principles of Bone Cancer Management nique that has been used in the pretreatment staging
of soft tissue and bone sarcomas.31,32 Recent reports
Multidisciplinary Team Involvement in the literature have shown the utility of PET scans
Primary bone tumors and selected metastatic tu- in the evaluation of response to chemotherapy in
mors should be evaluated and treated by a multi- patients with osteosarcoma, ESFT, and advanced
disciplinary team of physicians with demonstrated chordoma.33–36 PET or PET/CT with the investiga-
expertise in the management of these tumors. Long- tional radioactive substance 18F-fluoromisonidazole
term surveillance and follow-up are necessary when (FMISO) has been shown to identify the hypoxic
considering the risk of recurrence and comorbidities component in residual chordomas before RT.37 This
NCCN Clinical Practice Guidelines in Oncology 707
Bone Cancer
approach is being evaluated in clinical trials and same principles should be applied for core needle and
would be helpful in identifying tumors with low oxy- open biopsy. Appropriate communication between
gen levels that are more resistant to RT. the surgeon, musculoskeletal oncologist, and bone
Biopsy pathologist is critical in planning the biopsy route. It
Incisional (open) and percutaneous biopsy (core is essential to select the biopsy route in collaboration
needle or fine-needle aspiration) are the techniques with the surgeon to ensure that the biopsy tract lies
used historically in the diagnosis of musculoskeletal within the planned resection bed so that it can be
lesions.38,39 Open biopsy is the most accurate method resected with the same wide margins as the primary
because of the larger sample size, which is useful for tumor during surgery. Although fine-needle aspira-
performing additional studies such as immunohisto- tion is not associated with a significant risk of tumor
chemistry or cytogenetics.40 However, open biopsy seeding, it is not suitable for the diagnosis of primary
requires general or regional anesthesia and an oper- lesions, because its diagnostic accuracy is less than
ating room, whereas core biopsy can be performed that of core needle biopsy.49
under local anesthesia, with or without sedation. Surgery
Core needle biopsy has also been used as an alterna- Surgical margins should be negative, wide enough
tive to open biopsy for diagnosing musculoskeletal to minimize potential local recurrence, and nar-
lesions, with accuracy rates ranging from 88% to row enough to maximize function. Wide excision
96% when adequate samples are obtained.41–44 Cost implies histologically negative surgical margins,
savings may be realized when needle biopsy is used and is necessary to optimize local control. Local tu-
in selected patients. 41 Recent advances in imaging mor control may be achieved either through limb-
techniques have contributed to the increasing use sparing resection or limb amputation. In selected
of image-guided percutaneous biopsy for the diag- cases, amputation may be the most appropriate op-
nosis of primary and secondary bone tumors.45 The tion to achieve this goal. However, limb-sparing re-
preferred method for biopsy remains controversial section is preferred if reasonable functional outcomes
because no randomized controlled trials have com- can be achieved. Final pathologic evaluation should
pared core needle biopsy with open biopsy. include assessment of surgical margins and size/
The guidelines recommend core needle or open dimensions of tumor. The response to the preopera-
biopsy to confirm the diagnosis of primary bone tu- tive regimen should be evaluated using pathologic
mor before any surgical procedure or fixation of pri- mapping. Consultation with a physiatrist is recom-
mary site. Biopsy should be performed at the center mended to evaluate for mobility training and to pre-
that will provide definitive treatment for patients scribe an appropriate rehabilitation program.
with a suspected primary malignant bone tumor. At
biopsy, careful consideration should be given to ap- Radiation Therapy
propriate stabilization of the bone and/or to measures RT is used either as an adjuvant to surgery for pa-
to protect against impending pathologic fracture. tients with resectable tumors or as definitive therapy
The placement of biopsy is critical to the planning in patients with tumors not amenable to surgery.
of limb-sparing surgery, and failure to follow appro- Specialized techniques such as intensity-modulated
priate biopsy procedures may lead to adverse patient radiation therapy (IMRT); particle beam RT with
outcomes.38,39 In a multicenter review of 597 patients protons, carbon ions, or other heavy ions; stereotac-
with musculoskeletal tumors, alteration of the treat- tic radiosurgery (SRS); or fractionated stereotactic
ment plan (complex resection or the use of adjunc- radiotherapy (FSRT) should be considered as clini-
tive treatment) was encountered in 19%, and unnec- cally indicated to deliver high radiation doses while
essary amputation was performed in 18 patients.46 maximizing normal tissue-sparing. RT should be
Both open and core needle biopsy techniques are administered at the same specialized center that is
associated with risk of local tumor recurrence, either providing surgical and systemic interventions. See
through spillage of tumor or tumor seeding along “Principles of Radiation Therapy” in the full version
the biopsy tract if the scar is not removed en bloc of these guidelines for treatment volumes and radia-
during tumor resection. The risk of tumor seeding tion doses specific to each subtype (to view the most
is less with core needle biopsy.47,48 Nevertheless, the recent version of these guidelines, visit NCCN.org).
Bone Cancer
Chordoma CT is also of particular importance to assess bony

Chordomas arise from the embryonic remnants involvement, calcifications, and soft tissue and epi-
of the notochord and are more common in older dural extension of spinal chordomas, whereas MRI
adults. Chordomas predominantly arise in the axial is the best imaging modality to detect tumor ex-
skeleton, with the sacrum (50%–60%), skull base tension, cord compression, local recurrence, and
(25%–35%), and spine (15%) the most common residual tumor in the surgical scar tissue after surgi-
primary sites.6,50 Chordomas are classified into 3 cal resection.60,61 CT scan is also useful in planning
histologic variants: conventional, chondroid, and the reconstruction of the resistant osseous defect in
dedifferentiated. Conventional chordomas are the tumors of the proximal sacrum.
Biopsy to confirm histologic subtype should be
most common histologic subtype, characterized by
performed after imaging studies and may vary de-
the absence of cartilaginous or mesenchymal com-
pending on the anatomic location of the tumor.
ponents. Chondroid chordomas present with histo-
Needle biopsy is not recommended for skull base tu-
logic features of chordoma and cartilage elements,
mors. Suspected sacral chordomas should be biopsied
accounting for 5% to 15% of all chordomas. De-
dorsally rather than transrectally.
differentiated chordomas constitute approximately
2% to 8% of all chordomas and have features of Treatment
high-grade spindle cell sarcoma and an aggressive Surgery: Wide excision with adequate margins is the
clinical course.50 preferred primary treatment for patients with chor-
Chordomas of the spine and sacrum present with doma.62,63 A recent retrospective analysis of 962 pa-
localized deep pain or radiculopathies, whereas cer- tients with chordoma identified in the SEER database
vical chordomas can cause airway obstruction or dys- demonstrated that surgery significantly improves the
phagia and might present as an oropharyngeal mass. overall survival (OS).63 Several other reports have
Neurologic deficit is more often associated with confirmed the prognostic significance of wide surgi-
chordomas of the skull base and mobile spine than cal margins, in terms of relapse-free survival and OS,
with chordomas of the sacrococcygeal region.6 in patients with chordomas of the sacrum,64–66 skull
base 67–71 and spine.66,72
Workup Among patients with chordoma of the mobile
Initial workup should include a history and physi- spine, Boriani et al72 reported that only margin-
cal examination with adequate imaging (radiograph, free en bloc resection was associated with continu-
CT, and MRI) of the primary site, screening MRI of ous disease-free survival (DFS) with a follow-up of
spinal axis, and CT scan of the chest, abdomen, and longer than 5 years; 12 of 18 patients were continu-
pelvis. PET scan or bone scan (if PET scan is nega- ously disease-free at an average of 8 years after en
tive) can be considered for unusual cases. Benign bloc resection, whereas all patients who were treated
notochordal cell tumors (BNCTs) are considered with intralesional excision experienced recurrences
precursors to chordomas and do not require surgical in less than 2 years. In patients with chordomas of
management.51,52 CT scan and MRI may be useful in the sacrum and spine, Ruggieri et al65 reported a lo-
distinguishing BNCTs from chordomas.53,54 cal recurrence rate of only 17% after wide surgical
For skull base chordomas, CT is useful to delin- margins compared with 81% after intralesional exci-
eate bone destruction and the presence of calcifi- sion or marginal surgery. Tzortzidis et al68 reported
cations, whereas MRI is the preferred modality for that aggressive microsurgical resection is associated
defining the tumor margin from brain, character- with long-term, tumor-free survival with good func-
izing the position and extension of tumors into the tional outcome in patients with cranial base chor-
adjacent soft tissue structures, and visualizing blood domas; gross total removal was achieved in 72% of
vessels.55,56 For sacrococcygeal chordomas, CT and patients, resulting in local control rates of 50%. In
MRI are useful for assessing soft tissue involvement, a recent 10-year meta-analysis that included 802
calcifications, and epidural extension.57–59 MRI patients with skull base chordomas, Di Maio et al71
provides more precise and superior contrast with reported that those with incomplete resection were
surrounding soft tissues compared with CT, and is 3.83 times more likely to experience a recurrence at
helpful to assess recurrent or metastatic lesions.57,58 5 years than those with complete resection.
Bone Cancer
Radiation Therapy: RT (preoperative, postop- mined based on RECIST criteria (complete response
erative, or intraoperative) is used in combination + partial response and stable disease ≥6 months) was
with surgery to improve local control and DFS for 64%, and the median progression-free survival (PFS)
patients with resectable sacral and skull base chor- in the intention-to-treat population was 9 months.36
domas.67,73–78 In a retrospective series involving 24 Imatinib in combination with cisplatin or sirolim-
patients with sacral and spine chordomas, combina- us has also been effective in small series of patients
tion of short-course preoperative RT, resection, and with advanced chordoma resistant to prior imatinib
reduced-field high-dose postoperative RT resulted in therapy.101,102 The efficacy of EGFR inhibitors such as
5-year DFS and local control rates of 54% and 72%, gefitinib, erlotinib, and cetuximab in patients with
respectively.75 In a more recent retrospective series of advanced chordoma resistant to imatinib has also
15 patients with sacrococcygeal chordoma who un- been demonstrated in case reports.103–105
derwent surgical treatment, intralesional resection NCCN Recommendations: Tumor location is the
with postoperative RT was associated with lower most important variable determining the choice of
local recurrence rates (20%) than extralesional re- primary treatment for patients with conventional
section without RT (100%, with a mean time to re- or chondroid chordomas. Dedifferentiated chordo-
currence of 2 years); the time to recurrence was also mas are usually managed as described in the NCCN
significantly longer in patients who received RT af- Guidelines for Soft Tissue Sarcoma (to view the most
ter surgery.77 RT in combination with surgery is also recent version of these guidelines, visit NCCN.org).
associated with improved local recurrence rates in Wide excision, with or without RT, is the pri-
patients with conventional or chondroid chordomas mary treatment option for patients with resectable
of the skull base.74,76 conventional or chondroid chordomas of the sacrum
Particle beam RT (either alone or in combina- and mobile spine.62,63 Intralesional excision with or
tion with photon beam RT) with high-energy pro- without RT (followed by MRI to assess the adequacy
tons79–87 or carbon ions88–92 has resulted in local con- of resection) is the preferred treatment for patients
trol rates ranging from 62% to 81% in patients with with resectable skull base tumors of conventional or
skull base and extracranial chordomas involving the chondroid histology. Maximal safe resection is recom-
spine and sacrum. In patients with sacral chordomas mended when appropriate.70 Adjuvant treatment with
tumors treated with a combination of high-energy RT can be considered for large extracompartmental
proton and photon beam RT, local control rates were tumors or for positive surgical margins after resection.
higher in patients with primary tumors compared Postoperative RT has been associated with improved
with those with recurrent tumors.85 Carbon ion RT local control and DFS after surgery with macroscopic
also resulted in preservation of urinary and anorec- surgical margins or intralesional excision.73,76,77,106,107
tal function compared with surgery in patients with Re-resection, if necessary, can be considered for skull
sacral chordomas.92 base tumors with positive surgical margins.
Specialized techniques such as IMRT, SRS, and RT is the primary treatment option for patients
FSRT have also been associated with good local con- with unresectable chordomas, irrespective of the tu-
trol rates in cranial and extracranial chordomas.93–97 mor location.
Systemic Therapy: Chordomas are not sensitive
Surveillance
to chemotherapy except for the potentially dedif-
Surveillance consists of a physical examination, im-
ferentiated portion of high-grade dedifferentiated
aging (radiograph, MRI with or without CT) of the
chordomas.98 Several signal transduction pathways,
including platelet-derived growth factor receptor, surgical site as clinically indicated, chest imaging
epidermal growth factor receptor (EGFR), and mam- (every 6 months for 5 years and annually thereafter),
malian target of rapamycin (mTOR), have been im- and annual cross-sectional abdominal imaging.
plicated in the pathogenesis of chordomas, leading Relapsed Disease
to the development of targeted therapies.99,100 Chordomas are characterized by a high rate of local
In a phase II trial of 56 patients with advanced recurrence, and distant metastases to lungs, bone,
chordoma treated with imatinib, 70% of patients soft tissue, lymph nodes, liver, and skin have been
had stable disease. The clinical benefit rate as deter- reported in up to 40% of patients with local recur-
Bone Cancer
rence.64,79,108,109 Among patients with recurrent chor- from 0% to 12% for wide excision and 12% to 65%
domas of skull base and spine, Fagundes et al79 re- for intralesional curettage. In some studies, the ex-
ported a higher 2-year actuarial OS rate for patients tent of intralesional excision and the tumor stage
treated with subtotal resection than those who re- have been identified as prognostic indicators for risk
ceived supportive care only (63% and 21%, respec- of recurrence.124–126 Blackley et al125 reported a lo-
tively; P=.001). However, some studies have reported cal recurrence rate of 12% in 59 patients who were
that surgery and RT are associated with lower local treated with curettage with high-speed burr and bone
control rates for recurrent tumors compared with pri- grafting, which was similar to that observed with the
mary tumors in patients with sacral chordomas.85,95 use of adjuvants; most of the patients had grade II or
Patients with recurrent disease can be managed III tumors. In another retrospective analysis of 137
with surgery and/or RT and/or systemic therapy. The patients, Prosser et al126 reported local recurrences in
guidelines have included imatinib with or without 19% patients after curettage as a primary treatment;
cisplatin or sirolimus and erlotinib with or without the local recurrence rate was only 7% for patients
cetuximab as systemic therapy options for patients with grade I and II tumors confined to the bone,
with recurrent tumors. compared with 29% for those with grade III tumors
with extraosseous extension.
Surgical adjuvants have been used in conjunc-
Giant Cell Tumor of the Bone tion with intralesional curettage to improve local
GCTB is a rare benign primary tumor of the bone, control rates. However, the findings from studies
accounting for approximately 3% to 5% of all pri- that have evaluated intralesional curettage with and
mary bone tumors, with a strong tendency for local without adjuvant in the same cohort of patients with
recurrence, which may metastasize to the lungs.110,111 primary or recurrent GCTB are inconsistent, with
GCTB usually occurs between 20 and 40 years of some reporting decreased local recurrence rates with
age. The distal femur and proximal tibia are the most the use of adjuvants.121,123,127–129 Others, however,
common primary sites. Malignant transformation to have reported no significant difference in local re-
high-grade osteosarcoma has been observed in rare currence rates with and without adjuvants.130–132
cases and is associated with a poor prognosis.112,113 Wide excision is also associated with poor func-
tional outcome and more surgical complications.133–137
Workup
Therefore, intralesional curettage is considered the
Initial workup should include a history and physi-
preferred treatment in most patients with stage I or II
cal examination with adequate imaging (radiograph,
tumors. Wide excision is usually reserved for more ag-
CT, and MRI) of the primary site. CT is useful to de-
gressive stage III tumors with extraosseous extension
fine the extent of cortical destruction, whereas MRI
or for otherwise unresectable tumors.126,138–141
is the preferred imaging modality to assess the exten-
Radiation Therapy: RT has been used either as a
sion of tumors into the adjacent soft tissue and neu-
primary treatment or in combination with surgery
rovascular structures.114,115 Chest imaging is essential
to improve local control and DFS for patients with
to identify the presence of metastatic disease. Bone
marginally resected, unresectable, progressive, or re-
scan can be considered for unusual cases. Biopsy is
current disease.142–152 In a recent retrospective analy-
essential to confirm the diagnosis. Brown tumor of
sis of 58 patients with GCTB (45 with primary tu-
hyperparathyroidism should be considered as a dif-
mor and 13 with recurrent tumor) treated with RT,
ferential diagnosis, although routine evolution of se-
the 5-year local control and OS rates were 85% and
rum calcium, phosphate, and parathyroid hormone
94%, respectively.151 Median follow-up was 8 years.
levels can help exclude this diagnosis.116
In this analysis, patient age was the only prognos-
Treatment tic factor associated with rates of local control (96%
Surgery: Wide excision and intralesional curettage for younger patients vs 73% for the older group),
are the 2 surgical treatment options for patients with OS (100% vs 87%), and DFS (96% vs 65%). Other
resectable tumors.117–123 Wide excision is associated studies have identified tumor size greater than 4 cm,
with a lower risk of local recurrence than intralesion- recurrent tumors, and RT doses of 40 Gy or less as
al curettage, with the local recurrence rates ranging negative prognostic factors for local control.147–149
Bone Cancer
Specialized techniques such as 3-dimensional tion; or RT are included as options for patients with
conformal RT and IMRT have also been associated unresectable metastases.
with good local control rates in patients with GCTB Surveillance
in locations that are not amenable to complete surgi- Surveillance should include a physical examination,
cal resection.153,154 imaging (radiograph, MRI with or without CT) of
NCCN Recommendations Localized Disease: Intra- the surgical site as clinically indicated, and chest im-
lesional excision with or without an effective adju- aging every 6 months for 2 years and then annually
vant is an adequate primary treatment for resectable thereafter.
tumors.130–132 Recurrent disease (local or metastatic) should be
Serial arterial embolizations have been shown managed as per primary treatment for localized dis-
to be effective in the management of patients with ease or metastatic disease at presentation.
giant cell tumors of the extremities, especially for
tumors with large cortical defects or joint involve-
ment, and those with large giant cell tumors of the Osteosarcoma
sacrum.155–158 A few case reports have reported the Osteosarcoma is the most common primary malig-
efficacy of interferon and pegylated interferon in the nant bone tumor in children and young adults.2 The
management of GCTB.159–162 More recently, results median age for all patients with osteosarcoma is 20
of a phase II study of denosumab (a fully humanized years. In adults older than 65 years, osteosarcoma
monoclonal antibody against the RANK ligand) develops as a secondary malignancy related to Paget
showed significant activity in patients with unresect- disease of the bone.16
able or recurrent GCTB, resulting in tumor response Osteosarcoma constitutes a family of lesions with
(defined as the elimination of at least 90% of giant a variety of histologic features and natural histories.
cells or no radiologic progression of the target lesion Osteosarcomas are broadly classified into intramed-
for up to 25 weeks) in 86% (30 of 35) of evaluable ullary, surface, and extraskeletal.167 High-grade intra-
patients.163,164 medullary osteosarcoma is the classic or convention-
For patients with lesions that are resectable with al form, constituting nearly 80% of osteosarcomas.167
unacceptable morbidity or unresectable axial lesions, It is a spindle cell tumor that produces osteoid or
the guidelines have included serial embolizations, immature bone. The most frequent sites are the me-
denosumab, interferon, or pegylated interferon as taphyseal areas of the distal femur or proximal tibia,
primary treatment options. RT has been associated which are the sites of maximum growth. Low-grade
with an increased risk of malignant transformation intramedullary osteosarcoma constitutes fewer than
and should be used in patients with tumors that are 2% of all osteosarcomas, and the most common sites
not amenable to embolization, denosumab, or inter- are similar to those of conventional osteosarcoma.168
ferons. Parosteal and periosteal osteosarcomas are jux-
After primary treatment, patients with stable/ tacortical or surface variants. Parosteal osteosar-
improved disease can be observed. For patients with comas are low-grade lesions accounting for up to
stable/improved disease with incomplete healing 5% of all osteosarcomas.168 The most common site
after primary treatment, intralesional excision is is the posterior distal femur. This variant tends to
recommended if the lesion has become resectable. metastasize later than the conventional form. Trans-
Patients with unresectable disease should be treated formation of low-grade parosteal osteosarcoma into
with denosumab. The guidelines recommend con- high-grade sarcoma has been documented in 24%
tinuation of denosumab until disease progression in to 43% of cases.169,170 Periosteal osteosarcomas are
patients experiencing response. intermediate-grade lesions most often involving the
Metastatic Disease: For patients presenting with re- femur followed by the tibia.168 High-grade surface
sectable metastases, the guidelines recommend that osteosarcomas are rare, accounting for 10% of all
the primary tumor be managed as described for lo- juxtacortical osteosarcomas.171,172 Pain and swelling
calized disease.110,111,165,166 Intralesional excision is are the most frequent early symptoms. Pain is often
recommended for resectable metastatic sites. Deno- intermittent in the beginning and a thorough work-
sumab, interferon, or pegylated interferon; observa- up sometimes is delayed because symptoms may be
Bone Cancer
confused with growing pains. Osteosarcoma spreads 4 times higher than the normal value, and 46% for
hematogenously, with the lung being the most com- patients with high values below this limit (P<.001).
mon metastatic site. However, in multivariate analysis, these markers did
Prognostic Factors not retain their prognostic significance when com-
Tumor site and size; patient age; presence and loca- pared with tumor volume, age, and histologic re-
tion of metastases; histologic response to chemo- sponse to chemotherapy.174,176
therapy; type of surgery; and surgical margins are Workup
significant prognostic factors for patients with os- Osteosarcomas present both a local problem and a
teosarcoma of the extremities and trunk.173–178 In an concern for distant metastasis. Initial workup should
analysis of 1702 patients with osteosarcoma of the include imaging of the primary site (MRI, with or
trunk or extremities treated in the Cooperative Os- without CT), chest imaging, PET scan, and/or bone
teosarcoma Study Group (COSS) protocols, patient scan. More detailed imaging (CT or MRI) of abnor-
age at diagnosis, tumor site, and primary metastases malities identified on primary imaging is required for
were identified as predictors of survival.175 In patients suspected metastatic disease.
with extremity osteosarcomas, size and location of Plain radiographs of osteosarcomas show cortical
the tumor within the limb at diagnosis also had a destruction and irregular reactive bone formation.
significant influence on outcome.175 All factors ex- Bone scan, although uniformly abnormal at the le-
cept age were significant in multivariate testing, with sion, may be useful to identify additional synchronous
surgical remission and histologic response to chemo- lesions. MRI provides excellent soft tissue contrast
therapy emerging as the key prognostic factors. In a and may be essential for operative planning. MRI is
recent report of the combined analysis of 3 European the best imaging modality to define the extent of the
Osteosarcoma Intergroup randomized controlled tri- lesion within the bone and soft tissues, detect “skip”
als, Whelan et al178 reported that good histologic re- metastases, and evaluate anatomic relationships
sponse to preoperative chemotherapy, distal location with the surrounding structures. In addition, ALP
(other than proximal humerus/femur), and female and LDH are frequently elevated in patients with os-
sex were associated with improved survival. teosarcoma. Serum LDH was significantly higher in
In patients with proven primary metastatic osteo- patients with metastatic disease at presentation than
sarcoma, the number of metastases at diagnosis and in patients with localized disease.176
the completeness of surgical resection of all clinically
detected tumor sites are of independent prognostic Treatment
value.24 Patients with one or a few resectable pulmo- Surgery: Surgery (limb-sparing surgery or amputa-
nary metastases have a survival rate that approaches tion) remains an essential part of management of
that of patients with no metastatic disease.179,180 patients with osteosarcoma.181 Studies that have
Elevated serum ALP and LDH levels have also compared limb-sparing surgery and amputation in
been identified as prognostic indicators in patients patients with high-grade nonmetastatic osteosarco-
with osteosarcoma.174,176,177 In a cohort of 1421 pa- ma have not shown any significant difference in sur-
tients with osteosarcoma of the extremity, Bacci et vival and local recurrence rates.182–184 However, limb-
al176 reported significantly higher serum LDH lev- sparing surgery is associated with better functional
els in patients with metastatic disease at presenta- outcomes.185 In patients with high-grade osteosarco-
tion than in those with localized disease (36.6% vs mas with good histologic response to neoadjuvant
18.8%; P<.0001). The 5-year DFS correlated with chemotherapy, limb-sparing surgery is considered
serum LDH level (39.5% for patients with high LDH the preferred surgical modality if wide surgical mar-
levels and 60% for those with normal values). In an- gins could be achieved.182,186 Amputation is gener-
other retrospective analysis of 789 patients with os- ally reserved for patients with tumors in unfavorable
teosarcoma of the extremity, Bacci et al177 reported anatomic locations not amenable to limb-sparing
that the serum ALP level was a significant prognostic surgery with adequate surgical margins.181,186
factor of event-free survival (EFS) in patients with Chemotherapy: The addition of adjuvant and neo-
osteosarcoma of extremity; the 5-year EFS rate was adjuvant chemotherapy regimens to surgery has im-
24% for patients with a serum ALP value more than proved outcomes in patients with localized osteo-
Bone Cancer
sarcoma. Early trials used chemotherapy regimens ed with neoadjuvant chemotherapy and surgery at
including at least 3 or more of the following drugs: the Rizzoli Institute, Bacci et al204 showed that the
doxorubicin, cisplatin, bleomycin, cyclophospha- 5-year DFS and OS correlated significantly with
mide or ifosfamide, dactinomycin, and high-dose histologic response to chemotherapy. The 5-year
methotrexate.187–192 Subsequent clinical trials have DFS and OS rates in good and poor responders were
demonstrated that short intensive chemotherapy 67.9% versus 51.3% (P<.0001) and 78.4% versus
regimens including cisplatin and doxorubicin with 63.7% (P<.0001), respectively. A report from the
or without high-methotrexate and ifosfamide pro- Children’s Oncology Group also confirmed these
duce excellent long-term results, similar to those findings; the 8-year postoperative EFS and OS rates
that have been achieved with multiagent chemo- were 81% and 87%, respectively, in good respond-
therapy.193–200 ers.203 The corresponding survival rates were 46%
In a randomized trial conducted by the European and 52%, respectively, in poor responders.
Osteosarcoma Group, the combination of doxorubi- The addition of muramyl tripeptide phospha-
cin and cisplatin was better tolerated compared with tidyl-ethanolamine (MTP-PE) to chemotherapy
a multidrug regimen, with no difference in survival has also been evaluated in patients with osteosar-
between the groups in patients with operable, non- coma.200,205 The addition of MTP-PE to chemo-
metastatic osteosarcoma.194 In both groups, the 3- therapy was associated with a statistically significant
and 5-year OS rates were 65% and 55%, respectively, improvement in 6-year OS (from 70% to 78%) and
and the 5-year PFS rate was 44%. In the INT-0133 a trend toward better EFS in patients with nonmeta-
study, which compared the 3-drug regimen (cispla- static resectable osteosarcoma.200 However, the im-
tin, doxorubicin, and methotrexate) with the 4-drug provement was not statistically different in patients
regimen (cisplatin, doxorubicin, methotrexate, and with metastatic disease.205 MTP-PE is not approved
ifosfamide) for the treatment of patients with non- by the FDA for the treatment of patients with osteo-
metastatic resectable osteosarcoma, no difference sarcoma.
was seen in 6-year EFS rates (63% and 64%, respec- Localized Disease
tively) and OS rates (74% and 70%, respectively) The guidelines recommend wide excision as the pri-
between the groups.200 mary treatment for patients with low-grade (intra-
Chemotherapy regimens without doxorubicin or medullary and surface) osteosarcomas and periosteal
cisplatin have also been evaluated in patients with lesions. Chemotherapy before wide excision could
localized osteosarcoma with the goal of minimizing be considered for patients with periosteal lesions.
long-term cardiotoxicity and ototoxicity.201,202 In a Although chemotherapy (neoadjuvant or adjuvant)
phase II study, the combination of cisplatin, ifos- has been used in the treatment of patients with peri-
famide, and epirubicin was active and reasonably osteal osteosarcoma, no data support that the addi-
well tolerated in patients with nonmetastatic osteo- tion of chemotherapy to wide excision improves out-
sarcoma of the extremity.201 With a median follow- come in patients with periosteal osteosarcoma.206,207
up of 64 months, the 5-year DFS and OS rates were In a review of 119 patients with periosteal sarcoma
41.9% and 48.2%, respectively. In another random- published by the European Musculoskeletal Oncol-
ized multicenter trial (SFOP-OS94), the combina- ogy Society, the use of neoadjuvant chemotherapy
tion of ifosfamide and etoposide resulted in a higher was not a prognostic factor, although it was used in
histologic response rate than the regimen containing most of the patients.207 More recently, Cesari et al206
high-dose methotrexate and doxorubicin (56% and also reported similar findings; the 10-year OS rate
39%, respectively). However, the 5-year OS was sim- was 86% and 83% for patients who received adju-
ilar in both arms and no significant difference was vant chemotherapy with surgery and those who un-
seen in 5-year EFS rates.202 Good histopathologic derwent surgery alone, respectively (P=.73). After
response (>90% necrosis) to neoadjuvant chemo- wide excision (of resectable lesions), the guidelines
therapy has been shown to be predictive of survival have included postoperative chemotherapy with a
regardless of the type of chemotherapy administered category 2B recommendation for patients with low-
after surgery.176,203 In an analysis of 881 patients with grade (intramedullary and surface) or periosteal sar-
nonmetastatic osteosarcoma of the extremities treat- comas with pathologic findings of high-grade disease.
Bone Cancer
Preoperative chemotherapy before wide excision at presentation.213–215 In a study of 57 patients with

is preferred for patients with high-grade osteosarco- metastatic disease at presentation treated with cis-
ma (category 1).193–202 Selected elderly patients may platin, doxorubicin, and a high dose of methotrexate
benefit from immediate surgery. After wide excision, and ifosfamide, the 2-year EFS and OS rates were
patients with a good histologic response (amount of 21% and 55%, respectively, compared with 75%
viable tumor <10% of the tumor area) should con- and 94% in patients with nonmetastatic disease at
tinue to receive several more cycles of the same che- presentation, treated with the same chemotherapy
motherapy. Patients with a poor response (viable tu- protocol.215
mor ≥10% of the tumor area) could be considered for Among patients with primary metastases treated
chemotherapy with a different regimen. However, in cooperative osteosarcoma trials, long-term surviv-
attempts to improve the outcome of poor respond- al rates were higher for those whose metastases were
ers through modifying the adjuvant chemotherapy excised after chemotherapy and surgery of the pri-
remain unsuccessful.208–211 Surgical re-resection with mary tumor compared with those whose metastases
or without RT can be considered for positive surgical could not be removed (48% and 5%, respectively).216
margins. An ongoing randomized trial of the Euro- The combination of aggressive chemotherapy with
pean and American Osteosarcoma Study Group is simultaneous resection of primary and metastatic le-
evaluating treatment strategies for resectable osteo- sions has also resulted in improved outcomes in pa-
sarcoma based on histologic response to preoperative tients with osteosarcoma of the extremity with lung
chemotherapy metastases at presentation.217
RT or adjuvant chemotherapy is recommended if For patients with resectable metastases (pul-
the sarcoma remains unresectable after preoperative monary, visceral, or skeletal) at presentation, the
chemotherapy. Proton beam RT has been shown to be guidelines recommend preoperative chemotherapy
effective for local control in some patients with unre- followed by wide excision of the primary tumor.
sectable or incompletely resected osteosarcoma.212 Chemotherapy and metastasectomy are included as
Chemotherapy should include appropriate options for the management of metastatic disease.
growth factor support (see the NCCN Guidelines for Unresectable metastatic disease should be managed
Myeloid Growth Factors for growth factor support; with chemotherapy and/or RT followed by reassess-
to view the most recent version of these guidelines, ment of the primary site for local control.
visit NCCN.org). A list of specific chemotherapy
regimens is available in “Bone Cancer Systemic Surveillance
Therapy Agents” on pages 702–703. Once treatment is completed, surveillance should
occur every 3 months for 2 years, then every 4
Metastatic Disease at Presentation
months for year 3, every 6 months for years 4 and 5,
Approximately 10% to 20% of patients present with and annually thereafter. Surveillance should include
metastatic disease at diagnosis.24,213 The number of
a complete physical, chest imaging, and imaging of
metastases at diagnosis and complete surgical resec-
the primary site. PET scan and/or bone scan (cat-
tion of all clinically detected tumor sites are of inde-
egory 2B) may also be considered. Functional reas-
pendent prognostic value in patients with primary
sessment should be performed at every visit.
metastatic disease at presentation.24 Unilateral me-
tastases and lower number of lung nodules were asso- Relapsed or Refractory Disease
ciated with improved outcomes with chemotherapy Approximately 30% of patients with localized dis-
in patients with synchronous lung metastases.179,180 ease and 80% of patients presenting with metastat-
The 2-year DFS rate was significantly higher for pa- ic disease will experience relapse. The presence of
tients with only 1 or 2 metastatic lesions than for solitary metastases, longer time to first relapse, and
those with 3 or more lesions (78% and 28%, respec- complete resectability of the disease at first recur-
tively).179 rence have been reported to be the most important
Although chemotherapy is associated with prognostic indicators for improved survival, whereas
improved outcomes in those with nonmetastatic patients not amenable to surgery and those with a
high-grade localized osteosarcoma, the results were second or a third recurrence have a poor progno-
significantly poorer in those with metastatic disease sis.218–222 In patients with primary nonmetastatic
Bone Cancer
osteosarcoma, a longer relapse-free interval to pul- months) was 29%. Partial response and stable disease
monary metastases was significantly associated with were seen in 8% and 34% of patients, respectively,
better survival.221 The prognostic significance of and were durable for 6 months or more in 17% of
surgical clearance among patients with second and patients.
subsequent recurrences was also confirmed in a re- The safety and efficacy of high-dose chemo-
cent report of survival estimates derived from large therapy/autologous stem cell transplantation has also
cohorts of unselected patients treated in the COSS been evaluated in patients with locally advanced,
group trials.223 metastatic, or relapsed sarcoma.233,234 In the Italian
The combination of etoposide with cyclophos- Sarcoma Group study, treatment with carboplatin
phamide or ifosfamide has been evaluated in clinical and etoposide followed by stem cell rescue, com-
trials.224,225 In a phase II trial of French Society of Pe- bined with surgery, induced complete response in
diatric Oncology, ifosfamide and etoposide resulted chemosensitive patients.234 Transplant-related mor-
in a response rate of 48% in patients with relapsed or tality was 3.1%. The 3-year OS and DFS rates were
refractory osteosarcoma.225 In another phase II trial, 20% and 12%, respectively. The efficacy of this ap-
cyclophosphamide and etoposide resulted in a 19% proach in high-risk patients has yet to be determined
response rate and a 35% rate of stable disease in pain prospective randomized studies.
tients with relapsed high-risk osteosarcoma.224 PFS The optimal treatment strategy for patients with
at 4 months was 42%. Single-agent gemcitabine and relapsed or refractory disease has not been defined. If
combination regimens such as docetaxel and gem- relapse occurs, patients should undergo second-line
citabine; cyclophosphamide and topotecan; and if- chemotherapy and/or surgical resection. Based on
osfamide, carboplatin, and etoposide have also been the results of the recent phase II trial, the guidelines
effective in the treatment of patients with relapsed have included sorafenib as a systemic therapy option
or refractory bone sarcomas.226–229 for patients with relapsed disease.232 A list of other
Samarium-153 ethylene diamine tetramethylene second-line chemotherapy regimens is provided in
phosphonate (153Sm-EDTMP), a bone seeking radio- “Bone Cancer Systemic Therapy Agents” on pages
pharmaceutical, has been evaluated in patients with 702–703. Surveillance is recommended for patients
locally recurrent or metastatic osteosarcoma or skel- responding to second-line therapy.
etal metastases.230,231 Anderson et al230 reported that Patients experiencing disease progression or re-
153
Sm-EDTMP with peripheral blood progenitor cell lapse after second-line therapy could be managed
support had low nonhematologic toxicity and pro- with resection, palliative RT, or best supportive care.
vided pain palliation for patients with osteosarcoma The guidelines have also included 153Sm-EDTMP as
local recurrences or osteoblastic bone metastases.230 an option. Participation in a clinical trial should be
Results of a recent dose-finding study also showed strongly encouraged.
that 153Sm-EDTMP can be effective in the treatment
of patients with high-risk osteosarcoma.231
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Individual Disclosures for the NCCN Bone Cancer Panel

Advisory Boards,
Speakers Bureau, Patent,
Expert Witness, Equity, or Date
Panel Member Clinical Research Support or Consultant Royalty Other Completed
Douglas R. Adkins, MD Amgen Inc.; Eisai Inc.; and None None None 3/28/13
Threshold Pharmaceuticals
Mark Agulnik, MD None None None None 4/6/12
Robert S. Benjamin, MD Amgen Inc. Amgen Inc. Johnson & None 3/28/12
Johnson;
Merck & Co.,
Inc.;
Pfizer Inc.
J. Sybil Biermann, MD None None None None 12/9/12
Brian Brigman, MD, PhD Lumicell Diagnostics; and Musculoskeletal None None 7/18/12
Musculoskeletal Transplant Transplant
Foundation Foundation
James E. Butrynski, MD None None None None 12/9/12
David Cheong, MD None None None None 2/26/13
Warren Chow, MD ARIAD Pharmaceuticals, Inc.; Novartis None None 8/7/12
Bristol-Myers Squibb Company; Pharmaceuticals
GlaxoSmithKline; Corporation; and
Novartis Pharmaceuticals Pfizer Inc.
Corporation; Hoffman-LaRoche;
and NCCN
William T. Curry, MD None None None None 3/29/12
Deborah A. Frassica, MD None None None None 4/3/13
Frank J. Frassica, MD None None None None 10/29/09
Francis J. Hornicek, MD, PhD None Stryker None AO Spine 2/3/12
Corporation
Kenneth R. Hande, MD ICON None None None 7/18/12
Francis J. Hornicek, MD, PhD None Stryker None AO Spine 2/3/12
Corporation
Robin L. Jones, MD, BS, MRCP None None None None 10/16/12
Joel Mayerson, MD Millennium Pharmaceuticals, Inc. None None None 4/30/13
Sean V. McGarry, MD None None None Musculoskeletal 8/8/12
Transplant
Foundation
Brian McGrath, MD None None None None 12/16/09
Carol D. Morris, MD, MS None None None None 8/8/12
Sujana Movva, MD None None None None 1/29/13
Richard J. O’Donnell, MD None None None None 3/27/13
R. Lor Randall, MD Children`s Oncology Group; Biomet; and None None 3/27/13
Connective tissue Oncology Musculoskeletal
Society; and Musculoskeletal Transplant
Tumor Society Foundation
Victor M. Santana, MD None None None None 7/29/12
Robert L. Satcher, MD, PhD None None None None 9/7/2011
Herrick J. Siegel, MD None None None None 8/19/12
Margaret von Mehren,MD Arog Pharmaceuticals; Eisai Inc.; Merck & None None 8/6/12
Astex; Eisai Inc.; Infinity; Co., Inc.; Novartis
Johnson & Johnson; Merck Pharmaceutical
& Co.; Morphotek; national Corporation;
Cancer Institute; Novartis Pfizer Inc.; and
Pharmaceutical Corporation; Pharma Mar
OSI Pharmaceuticals, Inc.; Pfizer,
Inc.; Pharma Mar; Sarcoma
Alliance for research through
Collaboration; and Synta
Pharmaceuticals Co.
The NCCN guidelines staff have no conflicts to disclose.

Referat Bone Sarcoma (Zihan Aulia Nugraha)

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688

Bone Cancer Primary bone cancers are extremely rare neoplasms

Abstract Please Note

These guidelines are also available on the Internet. For the

Journal of the National Comprehensive Cancer Network Bone

NCCN Bone Cancer Panel Members Joel Mayerson, MD¶τ

CHORDOMA Bone Cancer, Version 2.2013

WORKUP a,b HISTOLOGIC SUBTYPE

Conventional See Presentation and

a See Multidisciplinary Team (page 700).

Bone Cancer, Version 2.2013 CHORDOMA

PRESENTATION PRIMARY TREATMENT ADJUVANT TREATMENT

b See Principles of Bone Cancer Management (page 701).

CHORDOMA Bone Cancer, Version 2.2013

SURVEILLANCE RECURRENCE TREATMENT

b See Principles of Bone Cancer Management (page 701).

Bone Cancer, Version 2.2013 GIANT CELL TUMOR OF THE BONE

• History and physical examination

a Brown tumor of hyperparathyroidism should be considered as a differential diagnosis.

GIANT CELL TUMOR OF THE BONE Bone Cancer, Version 2.2013

See Primary Treatment for Localized Disease,

c Intralesional excision, with an effective adjuvant is adequate.

Bone Cancer, Version 2.2013 GIANT CELL TUMOR OF THE BONE

See previous page

OSTEOSARCOMA Bone Cancer, Version 2.2013

WORKUP a,b PRIMARY TREATMENT ADJUVANT TREATMENT

Metastatic disease See facing page

a See Multidisciplinary Team (page 700).

Bone Cancer, Version 2.2013 OSTEOSARCOMA

b See Principles of Bone Cancer Management (page 701).

OSTEOSARCOMA Bone Cancer, Version 2.2013

• See page 697 for

d See Bone Cancer Systemic Therapy Agents (pages 702-703).

Bone Cancer, Version 2.2013 OSTEOSARCOMA

d See Bone Cancer Systemic Therapy Agents (pages 702-703).

Bone Cancer, Version 2.2013

Specialists Critical in Certain Cases

Bone Cancer, Version 2.2013

PRINCIPLES OF BONE CANCER MANAGEMENT

Long-Term Follow-up and Surveillance/Survivorship

Bone Cancer, Version 2.2013

BONE CANCER SYSTEMIC THERAPY AGENTS

Giant Cell Tumor of Bone

• Second-line therapy (relapsed/refractory or metastatic disease)

BONE CANCER SYSTEMIC THERAPY AGENTS

Bone Cancer, Version 2.2013

BONE CANCER SYSTEMIC THERAPY AGENTS

Bone Cancer, Version 2.2013

PRINCIPLES OF RADIATION THERAPY

GIANT CELL TUMOR OF BONE

Treatment of Primary Tumor

Consider use of Stereotactic radiosurgery, especially for oligometastases

1 R0 = No microscopic residual disease, R1 = Microscopic residual disease, R2 = Gross residual disease

Bone Cancer, Version 2.2013

PRINCIPLES OF RADIATION THERAPY

Giant Cell Tumor of Bone

Mixed Histology Reports

Chordoma CT is also of particular importance to assess bony

Preoperative chemotherapy before wide excision at presentation.213–215 In a study of 57 patients with

Individual Disclosures for the NCCN Bone Cancer Panel

The NCCN guidelines staff have no conflicts to disclose.

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